Faculty Development Competitive Research Grant Program 2021-2023
Ligaments are fibrous tissues connecting bone-to-bone, and are prone to injuries upon excessive loading. Due to low vascularity and dynamic nature, injured ligaments do not have self-healing capacity, and surgical treatment is needed. Ligaments are composed mainly of collagen that provide elasticity as well as resistance to mechanical loadings. Research performed on human, bovine, and sheep Anterior Cruciate Ligament (ACL) demonstrated that collagen fibril diameter exhibits a bimodal (two-peak) and unimodal (normal) distribution for healthy and injured tissues, respectively. Based on this fact, the aims of this proposal are: i) forming a rat Anterior Cruciate Ligament (ACL) tear, and measuring the collagen fibril diameter distribution of healthy and injured bovine ACL, ii) fabricating scaffolds with diameter distributions mimicking those of healthy and injured bovine ACL tissues, and iii) performing in-vitro and in-vivo experiments for evaluating performance of scaffolds to see if they could serve as candidates of grafts for ACL reconstruction. We hypothesize that the scaffold mimicking the collagen fibril diameter distribution of healthy ACL will outperform, on the basis of native tissue, in terms of matrix production and distribution as well as tissue function. This study is designed to better understand the cell behavior in injured ACL tissues such that new approaches could be developed for enhanced ACL repair or regeneration. Earlier, healthy and injured ACL tissues obtained from human, sheep and bovine (by our research group) were investigated for collagen fibril diameter distribution, yet no prior attempt is available for rat ACL tissue. There is abundant literature for the fabrication of scaffolds with unimodal fiber diameter distribution (e.g., scaffolds with mean diameter of 80nm or 180nm) and culturing cells of different origin on these scaffolds. However, no data are available for the fabrication of fibrous scaffolds possessing bimodal distribution (e.g., scaffolds with peak diameters of 80nm and 180nm). Due to absence of such scaffolds, it has not been possible to date to fully understand the behavior of ACL cells in injured/healing tissues. The novelty in this study is that it proposes for the first time to i) measure collagen fibril diameter distribution of healthy and injured rat ACL tissue, ii) fabricate scaffolds to both qualitatively and quantitatively mimic the distribution of the native tissues, and iii) investigate the in vitro and in vivo performance of such scaffolds to serve as useful data for large animal or clinical studies aiming at ACL regeneration. The scaffolds will be produced by electrospinning of solutions of polycaprolactone (PCL) either on a rotating drum or a stationary platform. Bimodal scaffolds will be produced by simultaneous electrospinning of solutions having different concentrations. The outcomes of this study are expected to have significant scientific, technological and socio-economic contributions to the society. A significant outcome will be understanding the cell behavior on scaffolds representing the injured and healthy ACL collagen fibril diameter distribution. This will help developing new methods and approaches for the ACL regeneration. In a broader sense, the scaffolds to be utilized in this study are likely to find clinical applications for more than 175,000 people suffering from ACL related injuries each year, with a cost of $17-25K/patient.
|Short title||Bimodal nanofiber grafts for ACL reconstruction|
|Effective start/end date||1/1/21 → 12/31/23|
- Anterior Cruciate Ligament
- Diameter distribution
- Collagen fibril
- in vivo
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